ANEMIA,ANDIRONDEFICIENCYANEMIA

ANEMIA,
IRON DEFICIENCY ,
AND IRON DEFICIENCY ANEMIA
A nemia is one of the most widespread public health
problems, especially in developing countries, and has important health and welfare, social, and economic consequences. These include impaired cognitive development, reduced physical work capacity, and in severe cases increased risk of mortality, particularly during the perinatal period. There is also evidence that anemia may result in reduced growth and increased morbidity. Given the magnitude of the problem, greater efforts are needed to
develop and implement programs both to prevent and to control anemia. In program development, it is essential to understand the differences between anemia, iron deficiency,and iron deficiency anemia, and to recognize that anemia can result both from nutrition-related causes and from inflammatory/infectious disease, as well as from blood loss.
Anemia can result
from nutrition-
related causes, in
particular iron
deficiency, from
inflammatory/
infectious disease,
and from blood loss.This statement was
prepared by Dr. Penelope
Nestel and Dr. Lena
Davidsson. It was
reviewed by the INACG
Steering Committee.
What is anemia?
Anemia is defined as a hemoglobin concentration lower than the established cutoff defined by the World Health Organization. This cutoff figure ranges from 110 g/L for pregnant women and for children 6 months–5 years of age, to 120 g/L for nonpregnant women, to 130 g/L for men.1 In addition to sex, age, and pregnancy status, other factors influence the cutoff values for hemoglobin concentration. These include altitude, race, and whether the indi-vidual smokes.1 Anemia can be diagnosed by analyzing the hemoglo-bin concentration in blood or by measuring the proportion of red blood cells in whole blood (hematocrit).
Hemoglobin is an iron-containing protein in red blood cells that carries oxygen from the lungs to cells throughout the body. Without sufficient oxygen the physical capacity of individuals is reduced. Iron deficiency and iron deficiency anemia
With adequate nutrition, a reserve of iron is stored in tissues and is used when insufficient iron is absorbed, for example, when dietary intakes are inadequate or bioavailability is low.* The size of the body’s iron reserve, mostly in the liver, is therefore an index of iron nutritional status. Iron deficiency occurs in three sequentially developing stages.
The first stage is depleted iron stores. This occurs when the body no longer has any stored iron but the hemoglobin concentration remains above the established cutoff levels. A depleted iron store is defined by a low serum ferritin concentration (<12 µg/L). It is important to note that because ferritin is an acute-phase reactant, its concentration in the blood increases in the presence of subclini-cal and clinical inflammatory/infectious diseases; thus, it cannot be used to accurately assess depleted iron stores in settings where poor health is common.
The second stage is known as iron-deficient erythropoiesis. Developing red blood cells have the greatest need for iron, and in
this stage the reduced transport of iron is associated with the development of iron-deficient erythropoiesis. However, the hemoglo-*Bioavailability refers to the degree to which iron is available for absorption in the gut and utilized for normal metabolic functions.
bin concentration remains above the established cut off levels. This condition is characterized by an increase in the transferrin recep-tor concentration and increased free protoporphyrin in red blood cells.
The third and most severe form of iron deficiency is iron deficiency anemia (IDA). IDA develops when the iron supply is inadequate for hemoglobin synthesis, resulting in hemoglobin concentrations
below the established cutoff levels. To diagnose IDA, measurements of iron deficiency as well as hemoglobin concentration are needed.For practical purposes, the first and second stages are often re-ferred to collectively as iron deficiency.
Other causes of anemia
Other nutrient deficiencies have been associated with anemia.These include deficiencies of vitamins A, B-6, and B-12, riboflavin,and folic acid,2 although not all of the causal pathways have been clearly established.
Besides specific nutrient deficiencies, general infections and chronic diseases including HIV/AIDS, as well as blood loss, can cause anemia. For example, the risk of anemia increases when individuals are exposed to malaria and helminth infections. There are also many other, rarer causes of anemia, the most common being genetic disorders such as the thalassemias.
Malaria, especially from the protozoan Plasmodium falciparum ,causes anemia by rupturing red blood cells and by suppressing the production of new red blood cells. Malaria does not, however, cause iron deficiency, because much of the iron in hemoglobin released from the ruptured cells stays in the body.
Helminths such as hookworms and flukes such as schistosomes can cause blood loss and therefore iron loss. Adult hookworms attach themselves to the gut wall, where the mature larvae and adult worms ingest both the gut wall and blood. Hookworms change
feeding sites every 4–6 hours and during feeding secrete anticoagu-lant, resulting in secondary blood loss from the damaged gut wall after the worms have stopped feeding. The number of adult hook-worms and the fecal egg count, which is an indirect estimate of the number of worms, are strongly correlated with the amount of blood lost, which if chronic can result in iron deficiency anemia.
The nematode Trichuris trichiura can cause anemia when the worm burden is heavy. Heavy infections also cause inflammation and dysentery, which in turn can cause further blood loss.
The trematode Schistosoma haematobium can cause significant urinary blood loss in severe infection. The effect of this blood loss can be significant even in moderate infections if the person is
young and already anemic. The eggs are wedged into capillaries by female worms when they are laid, and the mechanical movements of the body push them into the bladder wall. The emerging eggs rupture the bladder wall, causing blood to leak into the bladder. With Schistosoma mansoni, emerging eggs rupture the intestinal lining, resulting in the leakage of blood and other fluids and nutri-ents into the lumen.
Anemia from iron deficiency versus other causes
In developed countries iron deficiency is generally the major cause of anemia. Data from the United States3 showed that for each case of anemia, there were 2.5 cases of iron deficiency. There are, how-ever, no data to show that this ratio applies to other parts of the world where iron deficiency is not always the only or primary cause of anemia.
Studies in Côte d’Ivoire4 and Benin5 estimated that iron deficiency anemia accounted for about 50% of the anemia observed. In the
Côte d’Ivoire study, the proportion of anemic individuals with iron deficiency varied by age and sex. About 80% of the anemic pre-school-age children had iron deficiency anemia, compared with 50% of the school-age children and women and 20% of the men. Malaria and other infections or inflammatory disorders contributed significantly to the high prevalence of anemia, particularly in young children, but these infections and/or disorders and iron deficiency could not explain all of the anemia cases.
Two studies used a technique called attributable risk analysis to estimate the proportion of anemia cases in the study population that can be attributed to hookworm and malaria. In the first study, carried out on the Kenyan coast,6 76% of the preschool-age chil-dren were anemic (Hb<110 g/L) and 3% severely so (Hb<50 g/L). Only 4%, 3%, and 7% of the anemia in the study population—irrespective of whether the subjects had hookworm or not—were attributed to, respectively, hookworm infection, heavy hook-worm infection, and malaria. Among the children infected with hookworm in the study, however, 14%, 28%, and 18% of the anemia cases could be explained by, respectively, hookworm infec-tion, heavy hookworm infection, and malaria infection. Thus, in areas where the attributable risk of malaria or helminth infection to anemia is high, it is important to identify and treat these infections, especially in the most vulnerable segments of the population. The authors of the above study note that the low percentages attribut-able to malaria could be partially explained by the marked annual and seasonal variation in prevalence, which makes it difficult to capture the dynamic association between malaria and anemia. The same complexities apply in determining attributable proportions for helminth parasitemia and anemia.
In the second study involving attributable risk analysis, among Zanzibari schoolchildren,7 62% of the children were anemic, 3%were severely anemic, and 51% were iron-deficient anemic. The authors estimated that if hookworm infection could be eradicated,the prevalence of anemia could be reduced by as much as 25%,iron deficiency anemia by 35%, and severe anemia (Hb<70 g/L) by 73%. Ten percent or less of anemia and iron deficiency anemia was attributable to malaria, infection with the nematode Ascaris
lumbricoides , or stunting (a proxy indicator for a chronically poor diet).
A review of studies conducted between 1985 and 2000 among pregnant women in areas with Plasmodium falciparum malaria 8estimated that the population-attributable risk range for this type of malaria in pregnant women was 2–15% for moderate (Hb<100–110g/L) and severe (Hb<70–80 g/L) anemia.
Distinguishing between attributable risk for the entire population—whether or not infection is present—and attributable risk for
infected individuals can be important for evaluating program effec-tiveness. For example, if iron-fortified wheat flour is introduced in a hookworm- or malaria-endemic area where no control programs are in place, the prevalence of anemia might not be reduced signifi-cantly at the population level, so the program would be deemed unsuccessful. However, among those who are iron-deficient anemic but not infected, the program could be effective.
Summary
Anemia can be caused by iron deficiency or by other nutritional and health factors. The distinction between causes is important for two reasons:
•Hemoglobin measurements are important in diagnosing ane-
mia, but they are neither sensitive to nor specific to iron defi-ciency.
•The success of any intervention to correct and control anemia
depends on whether the intervention deals with the underlying causes. In many developing countries, it is unlikely that all anemia results from iron deficiency, because other nutritional deficiencies as well as malaria, heavy loads of some helminths,and other inflammatory/infectious diseases also cause anemia.Knowing the underlying causes of anemia will enable program
managers to identify which interventions need to be implemented to reduce the unacceptably high prevalence of anemia in many coun-tries. Where most of the anemia is not the result of iron deficiency,iron supplementation or the fortification of food with iron will be inadequate by themselves to prevent and control anemia.
References
1World Health Organization/United Nations University/UNICEF. Iron deficiency anaemia, assessment, prevention and control: a guide for programme managers. Geneva: WHO, 2001.
2Van den Broek NR, Letsky EA. Etiology of anemia in pregnancy in south Malawi. Am J Clin Nutr 2000;72(suppl):247S–256S.
3Dallman PR, Yip R, Johnson C. Prevalence and causes of anemia in the Unites States, 1976 to 1980. Am J Clin Nutr 1984;39:437–445.
4Staubli Asobayire F, Adou P, Davidsson L, et al. Prevalence of iron deficiency, with and without concurrent anemia, in population groups with
high prevalence of malaria and other infections: a study in Côte d’Ivoire.
Am J Clin Nutr 2001;74 776–782.
5Hercberg S, Chaulica M, Galan P, et al. Prevalence of iron deficiency and
iron deficiency anemia in Benin. Public Health 1988;102:73–83.
6Brooker S, Peshu N, Warn PA, et al. The epidemiology of hookworm
infection and its contribution to anemia among preschool children on the Kenyan Coast. Trans R Soc Trop Med Hyg 1999;93:240–246.
7Stoltzfus R, Chwaya HM, Tielsch JM, et al. Epidemiology of iron deficiency anemia among Zanzibari schoolchildren: the importance of hookworms. Am
J Clin Nutr 1997;65:153–159.
8Steketee RW, Nahlen BL, Parise ME, Menendez C. The burden of malaria
in pregnancy in malaria-endemic areas. Am J Trop Med Hyg 2001;61(suppl
1–2):28–35.
About INACG
The International Nutritional Anemia Consultative Group (INACG) is dedicated to reducing the prevalence of iron deficiency anemia and other nutritionally preventable anemias worldwide. It sponsors international meetings and scientific reviews and convenes task forces to analyze issues related to etiology, treatment, and prevention of nutritional ane-mias. Examination of these issues is important to the establishment of public policy and action programs.
INACG Steering Committee
Dr. John Beard Pennsylvania State University, USA
Dr. Frances R. Davidson, Secretary U.S. Agency for International Development, USA
Dr. Lena Davidsson, Chair Swiss Federal Institute of Technology, Switzerland Dr. Eva Hertrampf Micronutrients Lab, INTA, Chile
Dr. Marian Jacobs University of Cape Town, South Africa
Dr. Sean Lynch Eastern Virginia Medical School, USA
Dr. Rebecca J. Stoltzfus The Johns Hopkins University, USA
Dr. Olivia Yambi UNICEF- ESARO, Kenya
INACG Secretariat Staff
Suzanne S. Harris, Ph.D.Veronica I. Triana, MPH
This publication is made possible by support from Micronutrient Global Leadership, a project of the Office of Health, Infectious Disease and Nutrition, Bureau for Global Health, U.S. Agency for International Development, under Cooperative Agreement Number HRN-A-
00-98-00027-00.
March 2002Printed in the United States of America
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